Functionalized resins have found numerous applications recently as supports in solid phase synthesis, reagents or protecting groups in organic synthesis and supports for chromatography or catalysis. The reactions which are used in the functionalization of insoluble resins are similar to those carried out on soluble materials, but are usually more difficult to control and evaluate owing to the insolubility of the resins.
A large number of the functional resins which have been prepared to date were synthesized by chemical modifications of crosslinked polystyrene. It is known that solvent soluble resins are usually more reactive and often give better yields than their macroreticular counterparts.
Numerous publications indicate that it is not possible to prepare benzyllithium by reacting benzyl halides with alkyllithiums because of Wurtz coupling. Gilman & Haubein, J. Am. Chem. Soc. 66, 1515 (1944); Perrine & Rapoport, Analytical Chem. Vol. 20, 635, (1948); Organometallic Derivatives of the Main Group Elements by Azlett (ed.) (1972); The Chemistry of Organolithium Compounds by Wakefield, 153 (1976). In these failures no benzyllithium was obtained, only trans-Stilbene and Wurtz coupling products formed. Thus, a skilled artisan would assume that a reaction between a halo-methylated polystyrene with alkyllithiums would result in Wurtz coupling. One aspect of the present invention involves the discovery that polymer-bound benzyllithium can be prepared by reaction with an alkyllithium, if the starting halo-methylated resin has a crosslink density of at least 4 percent but less than 75 percent.
The prior art does disclose the preparation of nonpolymer-bound benzyllithium from both methylbenzyl ether and tris(benzyl) tin chloride. Gilman and McNinch, "Direct Preparation of Benzyllithium and Methylbenzyllithium in Tetrahydrofuran", Journal of Organic Chemistry, 26, 3723-5, (1961) and D. Seyferth et al, The Preparation of Organolithium Compounds by the Transmetalation Reaction, J. Organometal Chem., Vol. 2, 431-3, (1964). However, a polymer-bound benzyllithium preparation has not been reported by any of the numerous references concerned with the functionalization of polystyrene resins. The prior art does not suggest or disclose the reaction of at least 4 percent crosslinked halomethylated resin with alkyllithium to produce the valuable intermediate "polymer-bound benzyllithium."
One aspect of the present invention is directed to the discovery that polymers consisting essentially of the monomers:styrene, vinyl benzyl chloride and divinylbenzene, that have a crosslinking (divinylbenzene content) of at least 4 but not more than 75 percent (by weight) will undergo a direct lithiation process without extensive Wurtz coupling.
Previous investigators have prepared functionalized polymers via copolymerization of substituted styrene monomers plus styrene and/or divinylbenzene to give the functionalized polymers directly. Introduction of functional groups onto styrene polymers by copolymerization of suitably functionalized styrene monomers is often difficult due to the insolubility or reactivity of the functionalized monomers. Further, reactivity differences may cause blocks to form which will result in the formation of undesirable polymers.